Cognitive function and diffusion tensor imaging were assessed in a group of 12 patients with early relapsing-remitting multiple sclerosis (disease duration <or=3 years), and mild clinical disability (expanded disability status scale <or=2), as well as in 12 control subjects. Patients showed impairment in immediate logical memory and delayed recall with the Rey auditory verbal learning test. No significant differences in classical executive tests were observed. In contrast, differences were found for specific executive tests including IOWA Gambling Task, multiple errands test hospital version (MET) and Hotel Task, as well as in Paced-Auditory Serial Addition Test (PASAT). Significant correlation was found between PASAT performance and FA measures (r = 0.64, P = 0.03), the apparent diffusion coefficients and the MET (r = 0.72, P = 0.01), as well as in one subtask of Hotel (r = -0.68, P = 0.02). Thus, executive deficits can best be appreciated at early stages of MS when a more specific battery of tests is used for patient evaluation. In this series, test failures observed correlated with changes in fronto-subcortical fiber tracts.